ArticleFrontiers in immunology2026
Serum metabolomic signatures predict clinical outcomes in advanced non-small cell lung cancer treated with pembrolizumab plus platinum-based chemotherapy.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Predicting response to pembrolizumab plus chemotherapy in advanced non-small cell lung cancer (NSCLC) remains challenging. Serum metabolomics offers a promising approach to identify biomarkers capturing host-tumor metabolic interactions. Methods: We conducted nuclear magnetic resonance (NMR) spectroscopy-based metabolomic analysis on 216 longitudinal serum samples from 36 patients with advanced NSCLC receiving first-line pembrolizumab plus chemotherapy. We examined how baseline and dynamic metabolite profiles related to survival and impending disease progression, applying multivariate analyses and Random Forest (RF) modelling. Results: Lower serum levels of branched-chain amino acids (BCAAs) valine and isoleucine were associated with disease progression within 60 days. Overall survival was linked to distinct metabolomic signatures: long-term survivors showed higher serum levels of various lipids, including total phospholipids, sphingomyelin, and apolipoproteins A1 and A2. In contrast, patients who died during follow-up had higher inflammatory markers, including glycoprotein acetyls and mannose. An RF model predicted survival status with high accuracy (AUC = 0.93), with sphingomyelin, apolipoprotein A2, and glycoprotein acetyls B among the top contributors. Conclusion: Serum metabolomic profiles are closely linked to clinical outcomes in advanced NSCLC treated with pembrolizumab plus chemotherapy. Key metabolites - particularly BCAAs, lipids, and inflammatory markers - emerge as promising non-invasive biomarkers for predicting progression and survival.
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